CN117653793A - Preparation method of porous hydroxyapatite microsphere modified PMMA bone cement, product and application thereof - Google Patents
Preparation method of porous hydroxyapatite microsphere modified PMMA bone cement, product and application thereof Download PDFInfo
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- CN117653793A CN117653793A CN202311741934.6A CN202311741934A CN117653793A CN 117653793 A CN117653793 A CN 117653793A CN 202311741934 A CN202311741934 A CN 202311741934A CN 117653793 A CN117653793 A CN 117653793A
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- 239000002639 bone cement Substances 0.000 title claims abstract description 81
- 239000004005 microsphere Substances 0.000 title claims abstract description 63
- 229910052588 hydroxylapatite Inorganic materials 0.000 title claims abstract description 60
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 title claims abstract description 60
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims abstract description 50
- 239000004926 polymethyl methacrylate Substances 0.000 claims abstract description 50
- 239000000843 powder Substances 0.000 claims abstract description 30
- 239000000243 solution Substances 0.000 claims abstract description 27
- 108010010803 Gelatin Proteins 0.000 claims abstract description 23
- 229920000159 gelatin Polymers 0.000 claims abstract description 23
- 239000008273 gelatin Substances 0.000 claims abstract description 23
- 235000019322 gelatine Nutrition 0.000 claims abstract description 23
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 23
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims abstract description 19
- 239000000839 emulsion Substances 0.000 claims abstract description 16
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000001354 calcination Methods 0.000 claims abstract description 9
- 238000004108 freeze drying Methods 0.000 claims abstract description 7
- 238000005406 washing Methods 0.000 claims abstract description 7
- 239000008346 aqueous phase Substances 0.000 claims abstract description 6
- 239000007864 aqueous solution Substances 0.000 claims abstract description 6
- 235000015112 vegetable and seed oil Nutrition 0.000 claims abstract description 5
- 239000008158 vegetable oil Substances 0.000 claims abstract description 5
- 239000007788 liquid Substances 0.000 claims description 30
- CGMRCMMOCQYHAD-UHFFFAOYSA-J dicalcium hydroxide phosphate Chemical compound [OH-].[Ca++].[Ca++].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-J 0.000 claims description 19
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 18
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 claims description 18
- 239000007790 solid phase Substances 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 13
- 238000002156 mixing Methods 0.000 claims description 13
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 9
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 9
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 9
- 239000000701 coagulant Substances 0.000 claims description 9
- 239000003999 initiator Substances 0.000 claims description 9
- 239000000178 monomer Substances 0.000 claims description 9
- GYVGXEWAOAAJEU-UHFFFAOYSA-N n,n,4-trimethylaniline Chemical compound CN(C)C1=CC=C(C)C=C1 GYVGXEWAOAAJEU-UHFFFAOYSA-N 0.000 claims description 9
- 239000003381 stabilizer Substances 0.000 claims description 9
- 229920002113 octoxynol Polymers 0.000 claims description 8
- 239000002504 physiological saline solution Substances 0.000 claims description 8
- 230000000630 rising effect Effects 0.000 claims description 7
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 6
- 239000011812 mixed powder Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- 238000004132 cross linking Methods 0.000 claims description 4
- 235000008390 olive oil Nutrition 0.000 claims description 4
- 239000004006 olive oil Substances 0.000 claims description 4
- 239000012071 phase Substances 0.000 claims description 4
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims 1
- 238000003760 magnetic stirring Methods 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 abstract description 19
- 230000009286 beneficial effect Effects 0.000 abstract description 4
- 230000005540 biological transmission Effects 0.000 abstract description 4
- 210000002449 bone cell Anatomy 0.000 abstract description 4
- 230000010261 cell growth Effects 0.000 abstract description 4
- 239000002207 metabolite Substances 0.000 abstract description 4
- 235000015097 nutrients Nutrition 0.000 abstract description 4
- 230000004071 biological effect Effects 0.000 abstract description 3
- 230000001105 regulatory effect Effects 0.000 abstract description 2
- 208000010392 Bone Fractures Diseases 0.000 description 5
- 206010017076 Fracture Diseases 0.000 description 4
- 208000001132 Osteoporosis Diseases 0.000 description 4
- 206010010214 Compression fracture Diseases 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 230000011164 ossification Effects 0.000 description 3
- 208000001164 Osteoporotic Fractures Diseases 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 230000001009 osteoporotic effect Effects 0.000 description 2
- 229910052712 strontium Inorganic materials 0.000 description 2
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010034156 Pathological fracture Diseases 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000003837 high-temperature calcination Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 206010041569 spinal fracture Diseases 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B25/00—Phosphorus; Compounds thereof
- C01B25/16—Oxyacids of phosphorus; Salts thereof
- C01B25/26—Phosphates
- C01B25/32—Phosphates of magnesium, calcium, strontium, or barium
- C01B25/327—After-treatment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/30—Particle morphology extending in three dimensions
- C01P2004/32—Spheres
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- Transplantation (AREA)
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Abstract
The invention relates to a preparation method of porous hydroxyapatite microsphere modified PMMA bone cement, a product and application thereof, wherein a mixed aqueous solution containing gelatin, alpha-TCP and hydroxyapatite is used as an aqueous phase solution, and is added into vegetable oil to obtain O/W emulsion; adding demulsifier, adding glutaraldehyde solution to crosslink gelatin, centrifuging to extract microsphere, washing, freeze drying and calcining to obtain porous hydroxyapatite microsphere; and adding the microspheres into PMMA powder to prepare the porous hydroxyapatite microsphere modified PMMA bone cement. The porous hydroxyapatite microsphere prepared by the invention has good biological activity, biocompatibility and bone conductivity, and micropores of the porous hydroxyapatite microsphere are beneficial to bone cell growth, nutrient transmission and metabolite discharge. The mechanical properties of the PMMA bone cement can be regulated and controlled by the modified PMMA bone cement.
Description
Technical Field
The invention relates to a method in the technical field of biomedical materials, in particular to a preparation method of porous hydroxyapatite microsphere modified PMMA bone cement, a product and application thereof.
Background
Osteoporosis (OP) is a common systemic bone metabolic disorder characterized by low bone mass and damage to bone microstructure tissue, which is prone to non-traumatic fractures. Osteoporotic vertebral compression fractures (osteoporotic vertebral compression fractures, OVCFs) are the most common osteoporotic fractures, accounting for about 45% of the osteoporotic fractures. Percutaneous vertebroplasty (percutaneous vertebroplasty, PVP) is the most commonly used minimally invasive technique for treating OVCFs, however, studies have reported that approximately 8% -52% of OVCFs patients undergo PVP post-surgery resulting in recurrent compression fractures (adjacent vertebral fracture, AVF) in the adjacent vertebral bodies. The reason is that the filling bone cement commonly used in PVP operation is PMMA bone cement, the bone cement has high mechanical strength but large elastic modulus and is not matched with the rigidity of the adjacent vertebral body; and has no bioactivity of stimulating bone formation, can not promote bone repair, and has poor fusion with surrounding bone tissue. Part of scholars are focused on researching bone cement materials and methods for locally improving osteoporosis after PVP operation, such as mixing element strontium into calcium phosphate bone cement, utilizing the effect of strontium in promoting osteoblast proliferation and osteogenesis activity to locally improve vertebral osteoporosis condition after PVP/PKP operation [ Lode, acta Biomaterialia, 2018], such as mixing mineralized collagen material into PMMA bone cement to construct bioactive MC-PMMA bone cement with high mechanical strength and osteogenesis effect [ Zhu, theranostics, 2020]. The mechanical property of PMMA bone cement is regulated and controlled to adapt to the bone characteristics of fracture or adjacent vertebral bodies, and the biocompatibility and bone promotion bioactivity of the PMMA bone cement are increased, so that the PMMA bone cement is a key direction for improving the clinical defects of PMMA.
Hydroxyapatite is a main inorganic component constituting bones and teeth of a human body, has the advantages of good bioactivity, biocompatibility, bone conductivity and the like, does not generate inflammatory reaction after being placed in a body, can be biodegraded, and is widely applied to clinical tissue engineering repair of orthopaedics, dentistry, plastic surgery and the like. Based on the research background, the porous hydroxyapatite microsphere is prepared by using an emulsion method and a high-temperature calcination method, micropores of the porous hydroxyapatite microsphere are beneficial to bone cell growth, nutrient transmission and metabolite discharge, and the porous hydroxyapatite microsphere is used as a filler to be mixed with PMMA powder to prepare PMMA bone cement with high bone promotion bioactivity and mechanical property matching.
Disclosure of Invention
The invention aims to provide a preparation method of PMMA bone cement modified by porous hydroxyapatite microspheres,
still another object of the present invention is: a PMMA bone cement product modified by the porous hydroxyapatite microsphere prepared by the method is provided.
Yet another object of the present invention is: there is provided the use of the above product.
The invention aims at realizing the following scheme: the preparation method of the porous hydroxyapatite microsphere modified PMMA bone cement comprises the following steps of:
(1) Preparing porous hydroxyapatite microspheres: adding a mixed aqueous solution containing gelatin, alpha-TCP and hydroxyapatite as an aqueous solution into vegetable oil containing a surfactant at 60 ℃ according to a volume ratio of 1:10-1:100 to obtain O/W type emulsion, continuously stirring until the alpha-TCP is solidified, transferring the emulsion into ice bath, adding physiological saline containing 0.1% triton-X as a demulsifier, simultaneously adding glutaraldehyde solution for further crosslinking gelatin, continuously stirring for 2 hours, centrifugally extracting microspheres, respectively washing the microspheres with ethanol and water for 3 times, freeze-drying the microspheres for more than 48 hours, and calcining the product in a muffle furnace at a temperature rising rate of 5 ℃/min for 4 hours at 1200 ℃ to obtain porous hydroxyapatite microspheres;
(2) Preparation of modified PMMA bone cement
The PMMA bone cement solid phase powder consists of 50-90% of PMMA prepolymer powder, 0.1-44% of porous hydroxyapatite microspheres, 5% of developer barium sulfate and 1-5% of initiator benzoyl peroxide; the curing liquid consists of 90-95% of MMA monomer, 4.9-9.9% of coagulant N, N-dimethyl p-toluidine and 0.1% of stabilizer hydroquinone, wherein the weight percentage is 100% of the sum, and the PMMA bone cement solid phase powder and the curing liquid are mixed according to the solid-liquid ratio of 1-1.5g/mL to obtain the porous hydroxyapatite microsphere modified PMMA bone cement.
The preparation method of the aqueous phase solution in the step (1) comprises the steps of adding alpha-TCP mixed powder containing 1-5% of hydroxyapatite into gelatin solution with the concentration of 5-15% (w/v) according to the solid-to-liquid ratio of 1.2-1.5mL/g, and magnetically stirring and dissolving the mixed powder at the temperature of 60 ℃.
The surfactant in the step (1) is one or more of Tween 20, tween 60, tween 80 and span 80.
The invention provides a PMMA bone cement modified by porous hydroxyapatite microspheres, which is prepared by any one of the above methods.
The invention provides application of porous hydroxyapatite microsphere modified PMMA bone cement in preparing a material required by high-activity mechanical controllable PMMA bone cement.
The mixed aqueous solution containing gelatin, alpha-TCP and hydroxyapatite is used as aqueous phase solution, and is added into vegetable oil to obtain O/W type emulsion; adding physiological saline containing 0.1% triton-X as demulsifier, adding glutaraldehyde solution to further crosslink gelatin, centrifuging to extract microsphere, washing with ethanol and water for 3 times, freeze drying, and calcining the product at 1200deg.C for 4 hr to obtain porous hydroxyapatite microsphere; and adding the microspheres into PMMA powder to prepare the porous hydroxyapatite microsphere modified PMMA bone cement.
The invention comprises the following steps:
1. an aqueous gelatin solution was prepared at 60℃at a concentration of 5-15% (w/v).
2. Adding alpha-TCP mixed powder with the mass fraction of the hydroxyapatite of 1-5% into the gelatin solution according to the solid-to-liquid ratio of 1.2-1.5mL/g to obtain an aqueous phase solution.
3. And adding the aqueous phase solution into vegetable oil containing a surfactant at 60 ℃ according to the volume ratio of 1:10-1:100 to obtain O/W type emulsion, and continuously stirring until alpha-TCP is solidified.
4. Transferring the emulsion into ice bath, adding physiological saline containing 0.1% triton-X as demulsifier, adding glutaraldehyde solution to crosslink gelatin, and stirring for 2 hr.
5. Centrifuging to extract microspheres, washing with ethanol and water respectively for 3 times, and freeze drying for more than 48 h.
6. Calcining the product in a muffle furnace at a temperature rising rate of 5 ℃/min for 4 hours at 1200 ℃ to obtain the porous hydroxyapatite microsphere.
7. The PMMA bone cement solid phase powder consists of 50-90% of PMMA prepolymer powder, 0.1-44% of porous hydroxyapatite microspheres, 5% of developer barium sulfate and 1-5% of initiator benzoyl peroxide; the curing liquid consists of MMA monomer 90-95%, coagulant N, N-dimethyl p-toluidine 4.9-9.9% and stabilizer hydroquinone 0.1%. The percentages are mass fractions and the sum is 100%.
8. Mixing PMMA bone cement solid-phase powder and curing liquid according to the solid-liquid ratio of 1-1.5g/mL to obtain the porous hydroxyapatite microsphere modified PMMA bone cement.
The porous hydroxyapatite microsphere prepared by the invention has good biological activity, biocompatibility and bone conductivity, and micropores of the porous hydroxyapatite microsphere are beneficial to bone cell growth, nutrient transmission and metabolite discharge. The modified PMMA bone cement can regulate and control the mechanical property of the PMMA bone cement, so that the PMMA bone cement is suitable for bone fracture or bone characteristics of adjacent vertebral bodies, the biocompatibility and the bone promotion bioactivity of the PMMA bone cement are increased, the fusion of an implant and bone tissues is promoted, and the occurrence risk of the recompression fracture of the adjacent vertebral bodies is reduced.
The invention has the advantages that:
the porous hydroxyapatite microsphere has good biological activity, biocompatibility and bone conductivity, and micropores of the porous hydroxyapatite microsphere are beneficial to bone cell growth, nutrient transmission and metabolite discharge;
the porous hydroxyapatite microsphere modified PMMA bone cement can regulate and control the mechanical property of the PMMA bone cement, so that the PMMA bone cement is suitable for bone characteristics of fracture or adjacent vertebral bodies, meanwhile, the biocompatibility and the bone promotion bioactivity of the PMMA bone cement are increased, the fusion of an implant and bone tissues is promoted, and the occurrence risk of recompression fracture of the adjacent vertebral bodies is reduced.
Drawings
FIG. 1 is a graph showing the compressive strength mechanics of the porous hydroxyapatite microsphere modified PMMA bone cement prepared in example 1.
Detailed Description
The following examples are given with the invention as defined by the detailed description and the specific procedures, but the scope of the invention is not limited to the following examples.
Example 1
A porous hydroxyapatite microsphere modified PMMA bone cement is prepared by the following steps:
(1) Preparing porous hydroxyapatite microspheres:
dissolving 0.5g of gelatin in 10mL of pure water, adding 7.68g of alpha-TCP and 0.32g of hydroxyapatite into the gelatin solution, uniformly mixing to obtain a water phase solution, adding the water phase solution into 300mL of olive oil containing 3g of span-80 to obtain O/W type emulsion, and continuously stirring until the alpha-TCP is solidified;
transferring the emulsion into ice bath, adding 300mL of physiological saline containing 0.1% triton-X as demulsifier, simultaneously adding 500 mu L of 1% (w/v) glutaraldehyde solution for further crosslinking gelatin, continuously stirring for 2h, centrifugally extracting microspheres after the reaction is finished, respectively washing 3 times with ethanol and water, freeze-drying for more than 48h, and calcining the product in a muffle furnace at a temperature rising rate of 5 ℃/min for 4h at 1200 ℃ to obtain porous hydroxyapatite microspheres;
(2) The preparation of the modified PMMA bone cement comprises the following components in percentage by mass:
the PMMA bone cement solid phase powder consists of 60% of PMMA prepolymer powder, 30% of porous hydroxyapatite microspheres, 5% of developer barium sulfate and 5% of initiator benzoyl peroxide;
the curing liquid consists of 95% of MMA monomer, 4.9% of coagulant N, N-dimethyl-p-toluidine and 0.1% of stabilizer hydroquinone;
and mixing the PMMA bone cement solid-phase powder with the curing liquid according to the solid-liquid ratio of 1g/mL to obtain the porous hydroxyapatite microsphere modified PMMA bone cement.
FIG. 1 is a graph showing the compressive strength and mechanical properties of the porous hydroxyapatite microsphere modified PMMA bone cement prepared in the embodiment, wherein the elastic modulus reaches 590MPa.
Example 2
Step (2) preparation of the porous hydroxyapatite microsphere modified PMMA bone cement, wherein the preparation of the modified PMMA bone cement is the same as that of example 1, the preparation is carried out according to the following steps: in the step (1), the step of (a),
firstly, dissolving 0.5g of gelatin in 10mL of pure water, adding mixed powder of 0.14g of hydroxyapatite and 6.86g of alpha-TCP into the gelatin solution, uniformly mixing, adding into 100mL of olive oil containing 1g of span-80 to obtain O/W type emulsion, and continuously stirring until the alpha-TCP is solidified;
the emulsion was transferred into an ice bath, 100mL of physiological saline containing 0.1% triton-X was added as a demulsifier, and 500. Mu.L of 1% (w/v) glutaraldehyde solution was added thereto, and stirring was continued for 2 hours. After the reaction, the microspheres were extracted by centrifugation, washed 3 times with ethanol and water, and freeze-dried. Calcining the product in a muffle furnace at a temperature rising rate of 5 ℃/min for 4 hours at 1200 ℃ to obtain the porous hydroxyapatite microsphere.
Example 3
The preparation of the porous hydroxyapatite microsphere modified PMMA bone cement in the step (1) is the same as that in the example 1, and the preparation method comprises the following steps: in the step (2), the step of (C),
the PMMA bone cement solid phase powder consists of 70% of PMMA prepolymer powder, 20% of porous hydroxyapatite microspheres, 5% of developer barium sulfate and 5% of initiator benzoyl peroxide;
the curing liquid consists of 97% of MMA monomer, 2.9% of coagulant N, N-dimethyl-p-toluidine and 0.1% of stabilizer hydroquinone;
and mixing the PMMA bone cement solid-phase powder with the curing liquid according to the solid-liquid ratio of 1g/mL to obtain the porous hydroxyapatite microsphere modified PMMA bone cement.
Example 4
The preparation of the porous hydroxyapatite microsphere modified PMMA bone cement in the step (1) is the same as that in the example 1, and the preparation method comprises the following steps: in the step (2), the step of (C),
the PMMA bone cement solid phase powder consists of 50% of PMMA prepolymer powder, 40% of porous hydroxyapatite microspheres, 5% of developer barium sulfate and 5% of initiator benzoyl peroxide;
the curing liquid consists of 95% of MMA monomer, 4.9% of coagulant N, N-dimethyl-p-toluidine and 0.1% of stabilizer hydroquinone;
and mixing the PMMA bone cement solid-phase powder with the curing liquid according to the solid-liquid ratio of 1g/mL to obtain the porous hydroxyapatite microsphere modified PMMA bone cement.
Claims (9)
1. The preparation method of the porous hydroxyapatite microsphere modified PMMA bone cement is characterized by comprising the following steps of:
(1) Preparing porous hydroxyapatite microspheres: adding a mixed aqueous solution containing gelatin, alpha-TCP and hydroxyapatite as an aqueous solution into vegetable oil containing a surfactant at 60 ℃ according to a volume ratio of 1:10-1:100 to obtain O/W type emulsion, continuously stirring until the alpha-TCP is solidified, transferring the emulsion into ice bath, adding physiological saline containing 0.1% triton-X as a demulsifier, simultaneously adding glutaraldehyde solution for further crosslinking gelatin, continuously stirring for 2 hours, centrifugally extracting microspheres, respectively washing the microspheres with ethanol and water for 3 times, freeze-drying the microspheres for more than 48 hours, and calcining the product in a muffle furnace at a temperature rising rate of 5 ℃/min for 4 hours at 1200 ℃ to obtain porous hydroxyapatite microspheres;
(2) Preparation of modified PMMA bone cement
The PMMA bone cement solid phase powder consists of 50-90% of PMMA prepolymer powder, 0.1-44% of porous hydroxyapatite microspheres, 5% of developer barium sulfate and 1-5% of initiator benzoyl peroxide; the curing liquid consists of 90-95% of MMA monomer, 4.9-9.9% of coagulant N, N-dimethyl p-toluidine and 0.1% of stabilizer hydroquinone, wherein the weight percentage is 100% of the sum, and the PMMA bone cement solid phase powder and the curing liquid are mixed according to the solid-liquid ratio of 1-1.5g/mL to obtain the porous hydroxyapatite microsphere modified PMMA bone cement.
2. The preparation method of the porous hydroxyapatite microsphere modified PMMA bone cement according to claim 1, wherein the preparation method of the aqueous phase solution in the step (1) is characterized in that alpha-TCP mixed powder containing 1-5% of hydroxyapatite by mass is added into gelatin solution with the concentration of 5-15% (w/v) according to the solid-to-liquid ratio of 1.2-1.5mL/g, and the dissolution is assisted by magnetic stirring at 60 ℃.
3. The method for preparing the porous hydroxyapatite microsphere modified PMMA bone cement according to claim 1, wherein the surfactant in the step (1) is one or more of Tween 20, tween 60, tween 80 and span 80.
4. A method for preparing a porous hydroxyapatite microsphere modified PMMA bone cement according to any one of claims 1 to 3, comprising the steps of:
(1) Preparing porous hydroxyapatite microspheres:
dissolving 0.5g of gelatin in 10mL of pure water, adding 7.68g of alpha-TCP and 0.32g of hydroxyapatite into the gelatin solution, uniformly mixing to obtain a water phase solution, adding the water phase solution into 300mL of olive oil containing 3g of span-80 to obtain O/W type emulsion, and continuously stirring until the alpha-TCP is solidified;
transferring the emulsion into ice bath, adding 300mL of physiological saline containing 0.1% triton-X as demulsifier, simultaneously adding 500 mu L of 1% (w/v) glutaraldehyde solution for further crosslinking gelatin, continuously stirring for 2h, centrifugally extracting microspheres after the reaction is finished, respectively washing 3 times with ethanol and water, freeze-drying for more than 48h, and calcining the product in a muffle furnace at a temperature rising rate of 5 ℃/min for 4h at 1200 ℃ to obtain porous hydroxyapatite microspheres;
(2) The preparation of the modified PMMA bone cement comprises the following components in percentage by mass:
the PMMA bone cement solid phase powder consists of 60% of PMMA prepolymer powder, 30% of porous hydroxyapatite microspheres, 5% of developer barium sulfate and 5% of initiator benzoyl peroxide;
the curing liquid consists of 95% of MMA monomer, 4.9% of coagulant N, N-dimethyl-p-toluidine and 0.1% of stabilizer hydroquinone;
and mixing the PMMA bone cement solid-phase powder with the curing liquid according to the solid-liquid ratio of 1g/mL to obtain the porous hydroxyapatite microsphere modified PMMA bone cement.
5. The method for preparing porous hydroxyapatite microsphere modified PMMA bone cement according to claim 4, wherein in the step (1),
firstly, dissolving 0.5g of gelatin in 10mL of pure water, adding mixed powder of 0.14g of hydroxyapatite and 6.86g of alpha-TCP into the gelatin solution, uniformly mixing, adding into 100mL of olive oil containing 1g of span-80 to obtain O/W type emulsion, and continuously stirring until the alpha-TCP is solidified;
the emulsion was transferred into an ice bath, 100mL of physiological saline containing 0.1% triton-X was added as a demulsifier, and 500. Mu.L of 1% (w/v) glutaraldehyde solution was added thereto, and stirring was continued for 2 hours. After the reaction, the microspheres were extracted by centrifugation, washed 3 times with ethanol and water, and freeze-dried. Calcining the product in a muffle furnace at a temperature rising rate of 5 ℃/min for 4 hours at 1200 ℃ to obtain the porous hydroxyapatite microsphere.
6. The method for preparing porous hydroxyapatite microsphere modified PMMA bone cement according to claim 4, wherein in the step (2),
the PMMA bone cement solid phase powder consists of 70% of PMMA prepolymer powder, 20% of porous hydroxyapatite microspheres, 5% of developer barium sulfate and 5% of initiator benzoyl peroxide;
the curing liquid consists of 97% of MMA monomer, 2.9% of coagulant N, N-dimethyl-p-toluidine and 0.1% of stabilizer hydroquinone;
and mixing the PMMA bone cement solid-phase powder with the curing liquid according to the solid-liquid ratio of 1g/mL to obtain the porous hydroxyapatite microsphere modified PMMA bone cement.
7. The method for preparing porous hydroxyapatite microsphere modified PMMA bone cement according to claim 4, wherein in the step (2),
the PMMA bone cement solid phase powder consists of 50% of PMMA prepolymer powder, 40% of porous hydroxyapatite microspheres, 5% of developer barium sulfate and 5% of initiator benzoyl peroxide;
the curing liquid consists of 95% of MMA monomer, 4.9% of coagulant N, N-dimethyl-p-toluidine and 0.1% of stabilizer hydroquinone;
and mixing the PMMA bone cement solid-phase powder with the curing liquid according to the solid-liquid ratio of 1g/mL to obtain the porous hydroxyapatite microsphere modified PMMA bone cement.
8. A porous hydroxyapatite microsphere modified PMMA bone cement, characterized in that it is prepared according to the method of any one of claims 1 to 7.
9. The use of the porous hydroxyapatite microsphere modified PMMA bone cement according to claim 8 for preparing a material required by high activity mechanical controllable PMMA bone cement.
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